HIV-1 Envelope gp41 Antibodies Can Originate From Terminal Ileum B Cells That Share Cross-Reactivity With Commensal Bacteria

Cell Host Microbe. 2014 Aug 13;16(2):215-226. doi: 10.1016/j.chom.2014.07.003.

Abstract

Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibody Specificity
  • Antigens, Bacterial / immunology
  • Cross Reactions
  • HIV Antibodies / metabolism*
  • HIV Envelope Protein gp41 / immunology*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Ileum / immunology*
  • Ileum / pathology
  • Ileum / virology
  • Microbiota / immunology*
  • Molecular Sequence Data
  • Plasma Cells / immunology
  • Plasma Cells / virology
  • Protein Binding

Substances

  • Antigens, Bacterial
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • gp41 protein, Human immunodeficiency virus 1

Associated data

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